title: CAS/Crk coupling serves as a "molecular switch" for induction of cell migration.
abstract: Carcinoma cells selected for their ability to migrate in vitro showed enhanced invasive properties in vivo. Associated with this induction of migration was the anchorage-dependent phosphorylation of p130CAS (Crk-associated substrate), leading to its coupling to the adaptor protein c-CrkII (Crk). In fact, expression of CAS or its adaptor protein partner Crk was sufficient to promote cell migration, and this depended on CAS tyrosine phosphorylation facilitating an SH2-mediated complex with Crk. Cytokine-stimulated cell migration was blocked by CAS lacking the Crk binding site or Crk containing a mutant SH2 domain. This migration response was characterized by CAS/Crk localization to membrane ruffles and blocked by the dominant-negative GTPase, Rac, but not Ras. Thus, CAS/Crk assembly serves as a "molecular switch" for the induction of cell migration and appears to contribute to the invasive property of tumors.
authors.affiliation: Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA. klemke@scripps.edu
authors.forename: R L
authors.initials: RL
authors.lastname: Klemke
authors.forename: J
authors.initials: J
authors.lastname: Leng
authors.forename: R
authors.initials: R
authors.lastname: Molander
authors.forename: P C
authors.initials: PC
authors.lastname: Brooks
authors.forename: K
authors.initials: K
authors.lastname: Vuori
authors.forename: D A
authors.initials: DA
authors.lastname: Cheresh
mesh_terms: D000818:Animals; D019556:COS Cells; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D050719:Crk-Associated Substrate Protein; D005109:Extracellular Matrix / Q000502:physiology; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D015870:Gene Expression / Q000235:genetics / Q000502:physiology; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D008565:Membrane Proteins / Q000032:analysis; D009362:Neoplasm Metastasis; D010179:Pancreas / Q000166:cytology / Q000473:pathology / Q000503:physiopathology; D010190:Pancreatic Neoplasms / Q000473:pathology; D010750:Phosphoproteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D011506:Proteins; D011518:Proto-Oncogene Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D050737:Proto-Oncogene Proteins c-crk; D011817:Rabbits; D050717:Retinoblastoma-Like Protein p130; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism; D020744:rac GTP-Binding Proteins; D018631:ras Proteins / Q000737:chemistry / Q000378:metabolism; D018909:src Homology Domains
chemical_list: C493841:BCAR1 protein, human; D050719:Crk-Associated Substrate Protein; D007004:Hypoglycemic Agents; D007328:Insulin; D008565:Membrane Proteins; D010750:Phosphoproteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D050737:Proto-Oncogene Proteins c-crk; D050717:Retinoblastoma-Like Protein p130; D014443:Tyrosine; D019204:GTP-Binding Proteins; D020744:rac GTP-Binding Proteins; D018631:ras Proteins